Assessing Progression Independent of Relapse Activity in Multiple Sclerosis Using a Patient‐Reported Disability Measure and Self‐Administered Neuroperformance Outcomes

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Objective: The objective of this study was to investigate the ability of patient‐reported/administered outcomes to capture disability worsening and progression independent of relapse activity (PIRA) in multiple sclerosis (MS). Methods: We included patients from the longitudinal multicenter MS PATHS cohort with ≥3 assessments and >6 months follow‐up. PIRA was defined on the patient‐determined disease steps (PDDS) and self‐administered tests assessing walking speed, manual dexterity, and processing speed, in the absence of self‐reported relapses. We assessed (i) prevalence of PDDS/self‐administered test‐based disability worsening and PIRA definitions; (ii) their concurrent validity, through the association with worsening and PIRA definitions based on the expanded disability status scale (EDSS; Barcelona subcohort); and (iii) their clinical meaningfulness, through the correlation with brain magnetic resonance imaging (MRI) and quality‐of‐life (QoL) data trajectories. Results: We included 9,088 patients (73% female patients; age = 46.8 years; disease duration = 14.2 years). Over a 3‐year follow‐up, 4,066 (45%) patients worsened on ≥1 patient‐reported/administered outcome, of which 2,357 (58%) developed PIRA. In the Barcelona subcohort (N = 279), 68 (24%) patients developed EDSS‐based worsening, of which 30 (44%) developed EDSS‐based PIRA; 99 of 279 (35%) worsened on ≥1 patient‐reported/administered test, of which 78 of 99 (79%) had PIRA. Worsening (but not PIRA) on PDDS was associated with EDSS‐based worsening (odds ratio = 3.03 [1.42; 6.43], p = 0.004). PDDS/self‐administered‐test‐based worsening or PIRA strongly correlated with accelerated brain atrophy and T2 lesion volume increase compared to non‐worseners ( p < 0.05), and showed worse QoL ( p < 0.05). Interpretation: Despite only partial agreement with EDSS‐based definitions, PDDS/self‐administered test‐based worsening and PIRA definitions were clinically meaningful, by identifying patients with greater brain damage and poorer QoL, supporting their use in clinical practice. ANN NEUROL 2026;100:525–546

This publication has 43 references indexed in Scilit: